A Randomized Phase II Study of BAY 43-9006 in Combination With Gemcitabine in Metastatic Pancreatic Carcinoma

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed metastatic pancreatic
carcinoma

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral CT scan

- No prior chemotherapy for metastatic disease is allowed; prior adjuvant chemotherapy
is allowed provided that patients did not receive gemcitabine and the chemotherapy
completed > 6 months prior to initiation of study therapy

- Available tumor biopsy specimen (paraffin embedded or fresh frozen) that was obtained
at the time of diagnosis and/or prior to study entry is required

- Life expectancy of greater than 3 months

- ECOG performance status =< 1

- Leukocytes >= 3,000/μL

- Absolute neutrophil count >= 1,500/μL

- Platelets >= 100,000/μL

- Hemoglobin >= 9 mg/dL

- Total bilirubin =< 1.5 X institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) =< 3 X institutional upper limit of normal, unless the liver is
involved with tumor, in which the AST (SGOT)/ALT (SGPT) must be =< 5 X institutional
upper limit of normal

- Creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60
mL/min/1.73 m^2

- The effects of BAY 43-9006 on the developing human fetus at the recommended
therapeutic dose are unknown; for this reason and because raf kinase inhibitor agents
as well as other therapeutic agents used in this trial are known to be teratogenic,
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Because BAY 43-9006 is at least partially metabolized by the CYP 3A enzyme in the
liver, the possible effect that inhibitors of CYP 3A may have on BAY 43-9006 is
unknown; therefore, patients taking inhibitors of CYP 3A (such as ketoconazole,
itraconazole, and ritonavir) may not be enrolled in this study

- Patients may not be receiving any other investigational agents

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to BAY 43-9006 or gemcitabine

- Secondary primary malignancy (except in situ carcinoma of the cervix, in situ cancer
of the prostate, in situ cancer of the breast or adequately treated nonmelanomatous
carcinoma of the skin or other malignancy treated at least 5 years previously with no
evidence of recurrence); concurrent or history of another malignancy =< 5 years

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that
would limit compliance with study requirements

- Pregnant women are excluded from this study because BAY 43-9006 is a kinase inhibitor
agent with the potential for teratogenic or abortifacient effects; because there is
an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with BAY 43-9006, breastfeeding should be discontinued if the
mother is treated with BAY 43-9006

- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with BAY 43-9006; appropriate studies will be undertaken
in patients receiving combination anti-retroviral therapy when indicated

- Patients with evidence of bleeding diathesis

- Patients receiving therapeutic doses of anticoagulation; prophylactic anticoagulation
(i.e. low dose warfarin) of venous or arterial access devices is allowed